The objective of the proposed plan may be divided into two aspects; (1) the role of insulin in glucose and ion transport across the plasma membrane of "insulin sensitive" cells, and (2) the study of the ionic mechanisms involved in secretory control during stimulus-secretion coupling. These studies involve electrophysiological measurements using ion-selective microelectrodes. It has been widely reported that insulin can increase active Na ions-K ions transport and hyperpolarize "insulin sensitive" cells. The increase in intracellular K ions by these tissues has been used to explain the hypokalaemia associated with increases in blood insulin. Our findings, based on direct measurments with ion-selective microelectrodes in rat muscle and adipocytes, provide definitive evidence that insulin does not induce a change in membrane potential or ionic permeability. We have provided evidence that the epithelial cells of the blowfly salivary glands have the ability to buffer increases in free cytoplasmic Ca ions during the secretory process when stimulated with physiological concentrations of hormone. Our experiments also indicate that stimulation of these cells with higher than physiological concentrations of stimulus interferes with the normal intracellular Ca ion regulation and could lead to misinterpretation of the mechanism of stimulus-secretion coupling. We intend to define the electrochemical driving forces of Na ions. K ions, Ca ions and Cl ions involved in the stimulus-secretion coupling of glucose induced insulin release by isolated beta-islet cells.